Netrin 4 belongs to the netrins family, which are axons guiding molecules. To this day, 4 members of this family are known (netrins 1, G, 3, and 4). Netrin 4 is a protein consisting of a basic C-terminal domain interacting with heparin, 3 EGF-domains, and a laminin-domain (Yucchenco P D, Wadsworth W G (2004) Assembly and tissue functions of early embryonic laminins and netrins. Curr Opin Cell Biol. 16(5):572-9).
Patent application US 2003/0207347A1, published on Nov. 6, 2003, describes the native netrin 4 and uses thereof. More particularly, this application describes a netrin 4-derived polypeptide presenting properties for modulating angiogenesis, as well as the use of netrin 4 in a process of modulation of the vascular development, in particular of angiogenesis, and more particularly of inhibition of angiogenesis, in particular in tumors.
International patent application WO 2006/054000 describes the use of a mutated netrin 4 for the preparation of a drug for the prevention or the treatment of tumoral or non-tumoral pathologies, said mutated netrin 4 having an anti-angiogenic activity.
However, among sequences disclosed in this document, some improper mutated netrin 4 sequences comprise errors of sequencing.
An aim of the present invention is to provide new anti-angiogenic agents.
Another aim of the present invention is to provide a combination treatment allowing the increase of the treatments' efficiency involving angiogenesis, and in particular of usual anti-tumoral treatments, or of anti-angiogenic treatments used in pathologies other than tumors.
Until today, there is no known therapeutic agent able to interact with usual drugs as used for the treatment of age-related macular degeneration, or of other ocular diseases involving a neovascularization.